Medical Immunology Commons^™

Periodontal Health In A Large Cohort Of Ugandans Living With Hiv: A Cross-Sectional Study, William Buwembo, Adriane Kamulegeya, Dunstan Kalanzi, Priscilla Naava Namuyonga, Proscovia Nakasujja, David P. Katete, F. Collins Semitala, Catherine Mwesigwa-Lutalo, Samuel Kalungi, Jennifer E. Cameron, Ian G. Munabi

School of Medicine Faculty Publications

Background: The impact of periodontitis on large populations of people living with HIV (PLHIV) in resource-constrained settings remains largely un-investigated. This study aims to address this knowledge gap by providing a comprehensive description of the periodontal health status among a sizable cohort of Ugandans living with HIV. Methods: This was a cross-sectional study with 4,449 participants who were over 18-years old with data captured on their reported age, gender, tobacco use, length of time on HAART and alcohol use. Periodontal health was assessed using the WHO periodontal probe and the modified CPI data entry form. Descriptive statistics were reported using …

Excess Potassium Promotes Autophagy To Maintain The Immunosuppressive Capacity Of Myeloid-Derived Suppressor Cells Independent Of Arginase 1, Ramesh Thylur Puttalingaiah, Matthew J. Dean, Liqin Zheng, Phaethon Philbrook, Dorota Wyczechowska, Timothy Kayes, Luis Del Valle, Denise Danos, Maria Dulfary Sanchez-Pino

School of Medicine Faculty Publications

Potassium ions (K+) are critical electrolytes that regulate multiple functions in immune cells. Recent studies have shown that the elevated concentration of extracellular potassium in the tumor interstitial fluid limits T cell effector function and suppresses the anti-tumor capacity of tumor-associated macrophages (TAMs). The effect of excess potassium on the biology of myeloid-derived suppressor cells (MDSCs), another important immune cell component of the tumor microenvironment (TME), is unknown. Here, we present data showing that increased concentrations of potassium chloride (KCl), as the source of K+ ions, facilitate autophagy by increasing the expression of the autophagosome marker LC3β. Simultaneously, excess potassium …

Sex Hormones And Risk Of Lung And Colorectal Cancers In Women: A Mendelian Randomization Study, Marion Denos, Yi-Qian Sun, Ben Michael Brumpton, Yafang Li, Demetrius Albanes, Andrea Burnett-Hartman, Peter T Campbell, Sébastien Küry, Christopher I Li, Emily White, Jewel N Samadder, Mark A Jenkins, Xiao-Mei Mai

Faculty, Staff and Students Publications

The roles of sex hormones such as estradiol, testosterone, and sex hormone-binding globulin (SHBG) in the etiology of lung and colorectal cancers in women, among the most common cancers after breast cancer, are unclear. This Mendelian randomization (MR) study evaluated such potential causal associations in women of European ancestry. We used summary statistics data from genome-wide association studies on sex hormones and from the Trøndelag Health Study (HUNT) and large consortia on cancers. There was suggestive evidence of 1-standard deviation increase in total testosterone levels being associated with a lower risk of lung non-adenocarcinoma (hazard ratio 0.60, 95% confidence interval …

Tcellsi: A Novel Method For T Cell State Assessment And Its Applications In Immune Environment Prediction, Jing-Min Yang, Nan Zhang, Tao Luo, Mei Yang, Wen-Kang Shen, Zhen-Lin Tan, Yun Xia, Libin Zhang, Xiaobo Zhou, Qian Lei, An-Yuan Guo

Faculty, Staff and Student Publications

T cell is an indispensable component of the immune system and its multifaceted functions are shaped by the distinct T cell types and their various states. Although multiple computational models exist for predicting the abundance of diverse T cell types, tools for assessing their states to characterize their degree of resting, activation, and suppression are lacking. To address this gap, a robust and nuanced scoring tool called T cell state identifier (TCellSI) leveraging Mann-Whitney

Relative Effectiveness And Immunogenicity Of Quadrivalent Recombinant Influenza Vaccine Versus Egg-Based Inactivated Influenza Vaccine Among Adults Aged 18-64 Years: Results And Experience From A Randomized, Double-Blind Trial, Lauren Grant, Jennifer A Whitaker, Sarang K Yoon, Karen Lutrick, Shivam Bhargava, C Perry Brown, Emily Zaragoza, Rebecca V Fink, Jennifer Meece, Kristina Wielgosz, Hana El Sahly, Kurt T Hegmann, Ashley A Lowe, Alia Southworth, Tanya Tatum, Sarah W Ball, Min Z Levine, Matthew S Thiese, Steph Battan-Wraith, John Barnes, Andrew L Phillips, Alicia M Fry, Fatimah S Dawood, Randomized Assessment Of Influenza Vaccine Efficacy Network (Raiven)

Faculty, Staff and Students Publications

BACKGROUND: Immunogenicity studies suggest that recombinant influenza vaccine (RIV) may provide better protection against influenza than standard-dose inactivated influenza vaccines (SD IIV). This randomized trial evaluated the relative vaccine effectiveness (VE) and immunogenicity of RIV versus SD IIV in frontline workers and students aged 18-64 years.

METHODS: Participants were randomized to receive RIV or SD IIV and followed for reverse-transcription polymerase chain reaction (RT-PCR)-confirmed influenza during the 2022-2023 influenza season. Sera were collected from a subset of participants before and at 1 and 6 months postvaccination and tested by hemagglutination inhibition for A/H1N1, A/H3N2, B/Yamagata, and B/Victoria and against cell-grown …

High Fat, High Sucrose Diet Promotes Increased Expression Of Ace2 Receptor In The Siv-Infected Host: Implications For Sars-Cov-2 Infection, Elizabeth C. Delery, Danielle E. Levitt, Angela M. Amedee, Patricia E. Molina, Liz Simon

School of Graduate Studies Faculty Publications

Introduction: People with pre-existing conditions, including metabolic comorbidities, are at greater risk for complications of SARS-CoV-2 infection and expression of machinery required for viral entry into host cells may be a contributing factor. This study tested the hypothesis that high fat, high sucrose diet (HFSD) and alcohol use increase expression of angiotensin converting enzyme 2 (ACE2) receptor and transmembrane serine protease 2 (TMPRSS2) in tissues isolated from simian immunodeficiency virus (SIV) infected macaques, the most clinically relevant model for the study of HIV. Methods: Biospecimens obtained from a longitudinal study of SIV-infected, antiretroviral therapy (ART)-treated female rhesus macaques (Macaca mulatta) …

Creb-Binding Protein/P300 Bromodomain Inhibition Reduces Neutrophil Accumulation And Activates Antitumor Immunity In Triple-Negative Breast Cancer, Xueying Yuan, Xiaoxin Hao, Hilda L Chan, Na Zhao, Diego A Pedroza, Fengshuo Liu, Kang Le, Alex J Smith, Sebastian J Calderon, Nadia Lieu, Michael J Soth, Philip Jones, Xiang Hf Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Tumor-associated neutrophils (TANs) have been shown to promote immunosuppression and tumor progression, and a high TAN frequency predicts poor prognosis in triple-negative breast cancer (TNBC). Dysregulation of CREB-binding protein (CBP)/P300 function has been observed with multiple cancer types. The bromodomain (BRD) of CBP/P300 has been shown to regulate its activity. In this study, we found that IACS-70654, a selective CBP/P300 BRD inhibitor, reduced TANs and inhibited the growth of neutrophil-enriched TNBC models. In the bone marrow, CBP/P300 BRD inhibition reduced the tumor-driven abnormal differentiation and proliferation of neutrophil progenitors. Inhibition of CBP/P300 BRD also stimulated the immune response by inducing …

Exploring New Frontiers In Space Medicine: Unprecedented Detailed Mapping Of Human Biology During Spaceflight, Laura Ioana Patras, Nadia Houerbi, Jankeun Kim

FRONTIERS UNBOUND: Exploring Extreme Environments

No abstract provided.

Targeting Ribosome Biogenesis Is A Novel Approach For The Management Of Pancreatic Cancer, Mudassier Ahmad, Haider Ahsan, Carlos Perez, Muhammad Bangash, Andrew Massey, Emmanuel Anning, Manish Tripathi, Dae Kim, Subhash C. Chauhan, Bilal Bin Hafeez

Research Colloquium

Pancreatic ductal adenocarcinoma is the third leading cause of cancer-related deaths in the United States with limited therapeutic options available. Gemcitabine, a deoxycytidine nucleoside analog is currently considered the most effective therapy for PanCa. However, it shows only a marginal survival benefit of six months. Aberrant ribosome biogenesis occurs in most tumor types. We observed that PanCa cells are addicted to ribosome biogenesis, which supports their highly aggressive metastatic phenotypes. Thus, strategically targeting ribosome biogenesis process could be one of the ideal strategies for the prevention and treatment of PanCa. In this study, we elucidated the molecular mechanisms of POLR1A …

Role Of Poly(A)-Binding Protein Cytoplasmic 1, A Trna-Derived Rna Fragment-Bound Protein, In Respiratory Syncytial Virus Infection, Devin V Davis, Eun-Jin Choi, Deena Ismail, Miranda L Hernandez, Jong Min Choi, Ke Zhang, Kashish Khatkar, Sung Yun Jung, Wenzhe Wu, Xiaoyong Bao

Faculty, Staff and Students Publications

Respiratory Syncytial Virus (RSV) is a significant cause of lower respiratory tract infections (LRTI) across all demographics, with increasing mortality and morbidity among high-risk groups such as infants under two years old, the elderly, and immunocompromised individuals. Although newly approved vaccines and treatments have substantially reduced RSV hospitalizations, accessibility remains limited, and response to treatment varies. This underscores the importance of comprehensive studies on host-RSV interactions. tRNA-derived RNA fragments (tRFs) are recently discovered non-coding RNAs, notable for their regulatory roles in diseases, including viral infections. Our prior work demonstrated that RSV infection induces tRFs, primarily derived from the 5'-end of …

Fcrider: A Recombinant Fc Nanoparticle With Endogenous Adjuvant Activities For Hybrid Immunization, Changchuin Mao, Karen Eberle, Xiaojie Chen, Yiming Zhou, Jun Li, Hong Xin, Wenda Gao

School of Graduate Studies Faculty Publications

Active immunization (vaccination) induces long-lasting immunity with memory, which takes weeks to months to develop. Passive immunization (transfer of neutralizing antibodies) provides immediate protection, yet with high cost and effects being comparatively short-lived. No currently approved adjuvants are compatible with formulations to combine active and passive immunizations, not to mention their huge disparities in administration routes and dosage. To solve this, we engineered the Fc fragment of human IgG1 into a hexamer nanoparticle and expressed its afucosylated form in Fut8−/− CHO cells, naming it “FcRider.” FcRider is highly soluble with long-term stability, easily produced at high levels equivalent to those …

Complete Genome Sequence Of An Indian Outbreak Strain Of Chikungunya Virus, Eshna Laha, Deepak Jena, Viplov K. Biswas, Sharad Singh, Sunil K. Raghav, Asit K. Pattnaik, Soma Chattopadhyay

Nebraska Center for Virology: Faculty Publications

Here, we report the complete genome sequence of an Indian strain of chikungunya virus isolated from an infected patient from Hyderabad, Andhra Pradesh, India, during a massive outbreak in 2005–2006. The genome length spans 11,811 nucleotides and has a poly(A) tail of 29 residues at the 3′ end.

Characterization Of High-Risk-Other Human Papillomavirus Genotypes In Papanicolaou Tests, High-Grade Squamous Intraepithelial Lesions, And Cervical Cancer, Caitlin E. Witt, Elizabeth F. Sutton, Ashley M. Stansbury, Ashley N. Winters, Luke C. Konur, Meng Luo, Jennifer E. Cameron, Beverly Ogden

School of Medicine Faculty Publications

Background: The objective of this study was to determine the human papillomavirus (HPV) genotypes of high-risk-other HPV Papanicolaou (Pap) tests and of biopsy tissues from patients with high-grade squamous intraepithelial lesion (HGSIL) or cervical cancer. High-risk-other HPV status was determined with the cobas HPV Test (Roche Diagnostics, North America) that identifies 12 high-risk, non-16/18 HPV genotypes. We hypothesized that we would find genotypes of HPV in our population that are not covered by the 9-valent HPV vaccine. Methods: For this retrospective cohort study, we randomly selected 50 high-risk-other HPV Pap test samples from 2018 from our pathology department registries for …

A Systematic Review And Expert Delphi Consensus Recommendation On The Use Of Vaccines In Patients Receiving Dupilumab: A Position Paper Of The American College Of Allergy, Asthma And Immunology, Jay A Lieberman, Derek K Chu, Tasnuva Ahmed, Timothy E Dribin, Elissa M Abrams, Aikaterini Anagnostou, Kimberly G Blumenthal, Mark Boguniewicz, Nicole M Chase, David B K Golden, Nicholas L Hartog, Jennifer R Heimall, Tina Ho, Monica G Lawrence, David A Khan, Timothy Dean Minniear, S Shahzad Mustafa, John J Oppenheimer, Elizabeth J Phillips, Allison Ramsey, Nicholas L Rider, Lynda Schneider, Marcus S Shaker, Jonathan M Spergel, Cosby A Stone, David R Stukus, Julie Wang, Matthew J Greenhawt

Faculty, Staff and Students Publications

BACKGROUND: Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the …

Combination Therapy Of Ido1 Inhibition And Anti-Pd1 Mediates Anti-Tumor Immunity By Promoting Memory Immunity Development And Cytotoxicity Of Γδ T And Nk Cells Via Il-2 Signaling And By Overcoming Pro-Tumor Effects Of Tgf-Β Signaling, Hyuk Jee

Dartmouth College Master’s Theses

Cutaneous melanoma is the most aggressive form of skin cancer even though it takes only about 1% of all skin cancers. Even among all cutaneous melanomas, NRAS-mutant melanoma is more aggressive than any other, and about 10-25% of all cutaneous melanoma cases have mutations in NRAS. NRAS is a member of the RAS family of proto-oncogenic GTPase proteins, and it plays a key role in signal transduction pathways responsible for cellular survival, proliferation, and metabolism. Immunotherapy is the first line of defense against NRAS-mutant melanoma because, despite tremendous efforts made for decades, it has not been successful to develop small …

Facilitators And Barriers To Initiating And Completing Tuberculosis Preventive Treatment Among Children And Adolescents Living With Hiv In Uganda: A Qualitative Study Of Adolescents, Caretakers And Health Workers, Pauline Mary Amuge, Denis Ndekezi, Moses Mugerwa, Dickson Bbuye, Diana Antonia Rutebarika, Lubega Kizza, Christine Namugwanya, Angella Baita, Peter James Elyanu, Patricia Nahirya Ntege, Dithan Kiragga, Carol Birungi, Adeodata Rukyalekere Kekitiinwa, Agnes Kiragga, Moorine Peninah Sekadde, Nicole-Austin Salazar, Anna Maria Mandalakas, Philippa Musoke

Faculty, Staff and Students Publications

INTRODUCTION: People living with HIV (PLHIV) have a 20-fold risk of tuberculosis (TB) disease compared to HIV-negative people. In 2021, the uptake of TB preventive treatment among the children and adolescents living with HIV at the Baylor-Uganda HIV clinic was 45%, which was below the national target of 90%. Minimal evidence documents the enablers and barriers to TB preventive treatment (TPT) initiation and completion among children and adolescents living with HIV(CALHIV). We explored the facilitators and barriers to TPT initiation and completion among CALHIV among adolescents aged 10-19years and caretakers of children below 18years.

METHODS: We conducted a qualitative study …

Recurrent High Grade Serous Endometrial Cancer With Brain Metastases: Immunotherapy Confers Improved Quality Of Life And Survival, Kierany B. Shelvin, Jill Vincent, Shawna Morron, Michael Morin, Aaron Mammoser, Navya Nair

School of Medicine Faculty Publications

No abstract provided.

Epigenome-Wide Association Study Of Prostate Cancer In African American Men Identified Differentially Methylated Genes, Anders Berglund, Kosj Yamoah, Steven A. Eschrich, Rana Falahat, James J. Mulé, Sungjune Kim, Jaime Matta, Julie Dutil, Gilberto Ruiz-Deya, Carmen Ortiz Sanchez, Liang Wang, Hyun Park, Hirendra N. Banerjee, Tamara Lotan, Kathryn Hughes Barry, Ryan M. Putney, Seung Joon Kim, Clement Gwede, Jacob K. Kresovich, Youngchul Kim, Hui Yi Lin, Jasreman Dhillon, Ratna Chakrabarti, Jong Y. Park

School of Public Health Faculty Publications

Introduction: Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide. Methods: This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs. indolent PCa in 121 African American patients. Epigenome-wide DNA methylation patterns in tumor DNA were assessed using the human Illumina Methylation EPIC V1 array. Results: Around 5,139 differentially methylated CpG-sites (q < 0.01, lΔβl > 0.2) were identified when comparing normal vs. tumor, with an overall trend of hypermethylation in prostate tumors. Multiple representative differentially methylated regions (DMRs), including immune-related genes, such as CD40, Galectin3, OX40L, and STING, were detected …

Pre-Existing Immunocompromising Conditions And Outcomes Of Acute Covid-19 Patients Admitted For Pediatric Intensive Care, Courtney M Rowan, Brenna Labere, Cameron C Young, Laura D Zambrano, Margaret M Newhams, Suden Kucukak, Elizabeth R Mcnamara, Elizabeth H Mack, Julie C Fitzgerald, Katherine Irby, Aline B Maddux, Jennifer E Schuster, Michele Kong, Heda Dapul, Stephanie P Schwartz, Melania M Bembea, Laura L Loftis, Amanda R Kolmar, Christopher J Babbitt, Ryan A Nofziger, Mark W Hall, Shira J Gertz, Natalie Z Cvijanovich, Matt S Zinter, Natasha B Halasa, Tamara T Bradford, Gwenn E Mclaughlin, Aalok R Singh, Charlotte V Hobbs, Kari Wellnitz, Mary A Staat, Bria M Coates, Hillary R Crandall, Mia Maamari, Kevin M Havlin, Adam J Schwarz, Christopher L Carroll, Emily R Levy, Kristin L Moffitt, Angela P Campbell, Adrienne G Randolph, Janet Chou

Faculty, Staff and Students Publications

BACKGROUND: We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care.

METHODS: Fifty-five hospitals in 30 US states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients(PICU) or high-acuity unit for acute COVID-19 were included.

RESULTS: Of 1274 patients, 105 (8.2%) had an ICC, including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid-organ transplantation, 16 (15.2%) solid tumors, and 13 (12.4%) autoimmune disorders. Patients with ICCs were …

Pediatric Glioma Immune Profiling Identifies Tim3 As A Therapeutic Target In Braf Fusion Pilocytic Astrocytoma, Shashwat Tripathi, Hinda Najem, Corey Dussold, Sebastian Pacheco, Ruochen Du, Moloud Sooreshjani, Lisa Hurley, James P Chandler, Roger Stupp, Adam M Sonabend, Craig M Horbinski, Rimas V Lukas, Joanne Xiu, Giselle Lopez, Theodore P Nicolaides, Valerie Brown, Nitin R Wadhwani, Sandi K Lam, Charles David James, Ganesh Rao, Maria G Castro, Amy B Heimberger, Michael Decuypere

Faculty, Staff and Students Publications

Despite being the leading cause of cancer-related childhood mortality, pediatric gliomas have been relatively understudied, and the repurposing of immunotherapies has not been successful. Whole-transcriptome sequencing, single-cell sequencing, and sequential multiplex immunofluorescence were used to identify an immunotherapeutic strategy that could be applied to multiple preclinical glioma models. MAPK-driven pediatric gliomas have a higher IFN signature relative to other molecular subgroups. Single-cell sequencing identified an activated and cytotoxic microglia (MG) population designated MG-Act in BRAF-fused, MAPK-activated pilocytic astrocytoma (PA), but not in high-grade gliomas or normal brain. T cell immunoglobulin and mucin domain 3 (TIM3) was expressed on MG-Act and …